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Specific cellular uptake and sufficient drug release in tumor tissues are important for effective cancer therapy. Hyaluronic acid (HA), a skeleton material, could specifically bind to cluster determinant 44 (CD44) receptors highly expressed on the surface of tumor cells to realize active targeting. Cystamine (cys) is sensitive highly reductive environment inside tumor cells and was used as a connecting arm to connect docosahexaenoic acid (DHA) and chlorin e6 (Ce6) to the HA skeleton to obtain redox-sensitive polymer HA-cys-DHA/Ce6 (CHD). Nanoparticles were fabricated and loaded with chemotherapeutic drug docetaxel (DTX) by physical encapsulation. The prepared nanoparticles had significantly increased uptake by MCF-7 cells that overexpressed CD44 receptors, and DTX was effectively released at high reducing condition. Compared with mono-photodynamic therapy (PDT) or mono-chemotherapy, the prepared nanoparticles exhibited superior anti-tumor effect by inhibiting microtubule depolymerization, blocking cell cycle and generating reactive oxygen species (ROS). In vivo anti-tumor experiments proved that DTX/CHD nanoparticles had the best antitumor response versus DTX and CHD nanoparticles under near-infrared (NIR) irradiation. These studies revealed that redox-responsive DTX-loaded CHD nanoparticles held great potential for the treatment of breast cancer.

At present, malignant tumours have become one of the most serious diseases that endanger human health. According to a survey on causes of death in Chinese population in early 1990s, the malignant tumours were the second leading cause of death. In the treatment of tumours, the ideal situation is that drugs should target and accumulate at tumour sites and destroy tumour cells specifically, without affecting normal cells and stem cells with regenerative capacity. This requires drugs to be specifically transported to the target organs, tissues, cells, and even specific organelles, like mitochondria, nuclei, lysosomes, endoplasmic reticulum (ER), and Golgi apparatus (GA). The nano drug delivery system can not only protect drugs from degradation but also facilitate functional modification and targeted drug delivery to the tumour site. This article mainly reviews the targeting of nano drug delivery systems to tumour cytoplasmic matrix, nucleus, mitochondria, ER, and lysosomes. Organelle-specific drug delivery system will be a major mean of targeting drug delivery with lower toxicity, less dosage and higher drug concentration in tumour cells.

Sclerosing lipogranuloma (SLG) in children is a rare, benign disease of unknown etiology suspected to be due to abnormal fatty tissue reaction. A 13-year-old girl presented with progressively worsening back pain. Cross-sectional imaging identified a retroperitoneal mass compressing the left ureter as well as infrarenal inferior vena cava atresia with extensive venous collaterals and chronic partially occlusive thromboses of the iliac veins. Surgical biopsy was consistent with SLG and it resolved spontaneously. SLG is typically a disease of adulthood but may be seen in children. The association between inferior vena cava atresia with venous thrombosis and development of SLG has not been reported previously.

The selective infiltration of cell membranes and tissue barriers often blocks the entry of most active molecules. This natural defense mechanism prevents the invasion of exogenous substances and limits the therapeutic value of most available molecules. Therefore, it is particularly important to find appropriate ways of membrane translocation and therapeutic agent delivery to its target site. Cell penetrating peptides (CPPs) are a group of short peptides harnessed in this condition, possessing a significant capacity for membrane transduction and could be exploited to transfer various biologically active cargoes into the cells. Since their discovery, CPPs have been employed for delivery of a wide variety of therapeutic molecules to treat various disorders including cranial nerve involvement, ocular inflammation, myocardial ischemia, dermatosis and cancer. The promising results of CPPs-derived therapeutics in various tumor models demonstrated a potential and worthwhile scope of CPPs in chemotherapy. This review describes the detailed description of CPPs and CPPs-assisted molecular delivery against various tissues and organs disorders. An emphasis is focused on summarizing the novel insights and achievements of CPPs in surmounting the natural membrane barriers during the last 5 years.

Most of the potential therapeutic agents capable to modulate the pathophysiology or treat the neurological disorders and brain tumors are useless in the current modern and advanced era of neuroscience due to the impeding action of biological barriers. Among various therapeutic strategies applied for translocation of drug delivery across the blood-brain barrier (BBB), nanoformulations set an excellent platform for brain targeting by overcoming the biological and chemical barriers and protecting drug from efflux to promote the optimum therapeutic drug concentration in brain parenchyma tissues. Nanocarriers are the most widely studied delivery vehicles for BBB translocation with the efficiency of selectively targeting or exploiting inherent biological molecules, receptors, carriers or mechanisms of the brain. Nearly all of the available drug delivery nanocarriers explored in recent years for brain therapeutics and theranostics are based on lipid or polymeric materials. Polymeric nanoparticles (NPs) and lipid based nanocarriers including liposomes, solid lipid NPs (SLNs) and micelles, etc. are under the direct focus of neuroscientists due to the promising attributes and vast applications in neurological disorders. Surface modification of nanovehicles with proper targeting moiety or coating with surfactants promotes the interaction with endothelial cells and passage of nanocarriers to the brain. This review comprehensively depicts challenges to the brain targeted drug delivery, mechanisms of drug transportation across the BBB, and potential contributions of endogenous cells as NPs delivery cells and novel targeting ligands decorated nanoformulations in imaging, treating and controlling neurological disorders.

Multidrug resistance (MDR) of cancer is a persistent problem in chemotherapy. Scientists have considered the overexpressed efflux transporters responsible for MDR and chemotherapy failure. MDR extremely limits the therapeutic effect of chemotherapy in cancer treatment. Many strategies have been applied to solve this problem. Multifunctional nanoparticles may be one of the most promising approaches to reverse MDR of tumor. These nanoparticles can keep stability in the blood circulation and selectively accumulated in the tumor microenvironment (TME) either by passive or active targeting. The stimuli-sensitive or organelle-targeting nanoparticles can release the drug at the targeted-site without exposure to normal tissues. In order to better understand reversal of MDR, three main strategies are concluded in this review. First strategy is the synergistic effect of chemotherapeutic drugs and ABC transporter inhibitors. Through directly inhibiting overexpressed ABC transporters, chemotherapeutic drugs can enter into resistant cells without being efflux. Second strategy is based on nanoparticles circumventing over-expressed efflux transporters and directly targeting resistance-related organelles. Third approach is the combination of multiple therapy modes overcoming cancer resistance. At last, numerous researches demonstrated cancer stem-like cells (CSCs) had a deep relation with drug resistance. Here, we discuss two different drug delivery approaches of nanomedicine based on CSC therapy.

Background Lung cancer is the most common type of tumour worldwide. Its relative lethality is considerably high. However, since the tumour tissues are located deep within the human body, traditional technologies, such as photodynamic therapy, do not have the desired effect. Sonosensitisers can penetrate deeply into tissues, and sonodynamic therapy (SDT) effectively inhibits tumours by generating reactive oxygen species. Ultrasound can also penetrate deeply, with a favourable tumour inhibition effect. Results A redox/ultrasound-responsive Rhein-chondroitin sulphate-based nano-preparation encapsulating docetaxel was fabricated. The nanoparticles displayed increased cellular uptake with quick drug release, good stability, and a monodispersed form in the physiological environment. Rhein induced apoptosis and altered mitochondrial membrane potential, which enhanced the expression of apoptosis-related proteins. SDT inhibited the metastasis and angiogenesis of cancer cells and activated anti-tumour capacity by reducing the expression of M2 macrophages. Conclusions The potential of Rhein for SDT was demonstrated. Production of reaction oxygen species was markedly enhanced after ultrasound treatment. The nanoplatform enhanced the synergistic anti-tumour effects of SDT and chemotherapeutic efficacy. The approach was biocompatibility. The findings could inform investigations of chemo-SDT for different cancers.

Purpose: To compare recurrence rate of primary pterygium following excision with mitomycin c verses excisionwith amniotic membrane transplant.Study Design: Quasi experimental study.Place and Duration of Study: Qazi Hussain Ahmad Medical Complex, Nowshera, from January 2019 to June2019.Material and Methods: One hundred and two patients presenting for the first time with pterygium were includedin the study and were divided into two groups. Patients having conjunctivitis, blephritis, keratitis or any otherocular inflammatory condition and patients having history of chemical burns and symblepharon were excludedfrom the study. Group A underwent surgical excision with 0.02% mitomycin–C application for 3 minutes andGroup B was surgically treated with application of amniotic membrane. Patients of both groups were followed upfor six months to detect recurrence of pterygium. Data was analyzed using SPSS version 20. Frequency andpercentages were calculated for categorical data like age, gender and recurrence rate. Recurrence rate wasstratified among age and sex to see the effect modifiers.Results: Mean age in both groups was 39.98 ± 9.11 years. In group A, 64.70% patients were males and in groupB, 62.74% patients were male. Recurrence of Pterygium was seen in 21.5% patients in group A and 7.84% ingroup B. The difference was statistically significant with a p value of 0.05.Conclusion: Recurrence rate of primary pterygium following excision with mitomycin C is higher than excisionwith amniotic membrane transplant

Sonodynamic therapy (SDT) has been proposed as a new modality for cancer management through low-intensity ultrasound induced activation of sonosensitizers. Here, we designed a novel redox/enzyme/ultrasound responsive chondroitin sulfate-chlorin e6-lipoic acid nanoplatform loading docetaxel, combining SDT and chemotherapy, for antiproliferation and antimetastasis of melanoma. The reversibly crosslinked and self-assembled nanoparticles possessed monodispersive size distribution, stability in physical conditions, while showing increased uptake with rapid drug release in simulated tumor microenvironment (reductive potentials and degradative hyaluronidase-1). With synthesized ultrasound sensitive polymer backbones, SDT induced the generation of cellular reactive oxygen species and mitochondrial damage, exerting the apoptotic effect through the release of cytochrome C, the expression of cleaved caspase-9 followed by the functional cleaved caspase-3. Chemo-sonodynamic therapy not only inhibited tumor growth and metastasis with reduced metastatic protein expression, but also caused immune response via the release of tumor-associated antigens. It was initially demonstrated that SDT could induce the tumor cell death, therefore having potentials to recruit cytotoxic lymphocytes into tumor sites. Notably, the nanoplatforms exhibited good in vivo stability and blood compatibility, indicating the safety and efficiency in drug delivery. Our work thus presents a convenient approach to fabricate intelligent multifunctional nanoparticles and paves a path for effective cancer therapies.

Paclitaxel (PTX) belongs to a class of taxane anti-tumor drug used for the clinic treatment of breast cancer, ovarian cancer, non-small-cell lung cancer, and so on. PTX has poor water solubility and oral bioavailability. It is generally administered via intravenous (i.v.) infusion. Traditional PTX injectable preparations contain Cremophor-EL and ethanol to improve its solubility, which would result in adverse reactions like severe hypersensitivity, neutropenia, etc. Adverse reactions can be reduced only by complicated pretreatment with glucocorticoid and antihistamines drugs and followed by PTX slow infusion for three hours, which has brought significant inconvenience to the patients. Though, a new-generation PTX formulation, Abraxane, free of Cremophor-EL and ethanol, is still being administrated by frequent i.v. infusions and extremely expensive. Therefore, non-injection administration of PTX is urgently needed to avoid the side effects as well as reduce inconvenience to the patients. Recently, a variety of non-injection drug delivery systems (DDSs) of PTX have been developed. This review aims to discuss the progress of non-injectable administration systems of PTX, including oral administration systems, vaginal administration systems, implantable DDSs, transdermal DDSs and intranasal administration for the future study and clinical applications.

In this report, redox/enzyme responsive chondroitin sulfate-ss-deoxycholic acid (CSCD) conjugates were synthesized using cystamine as the linkage which could self-assemble to form self-assembled nanoparticles (175.6 + 5.2 nm) in the aqueous environment. Docetaxel (DTX) was loaded in nanoparticles with desired loading efficiency for the inhibition of tumor growth and metastasis of melanoma. Interestingly, nanoparticles were demonstrated to respond to hyaluronidase-1 (Hyal-1) which could degrade chondroitin sulfate (CS) backbones. In this case, we designed dual-sensitive nanoparticles with enhanced drug release pattern under the presence of glutathione (GSH)/Hyal-1. Compared with Taxotere®, CSCD nanoparticles significantly improved the DTX distribution in tumors and lungs with about 4.4-fold higher area-under-the-curve (AUC) value. In situ tumor volume and pulmonary metastatic formation were reduced upon the administration of DTX-loaded CSCD nanoparticles via DTX-induced apoptosis and decreased metastasis-promotion protein expression. With only minor cytotoxicity, CSCD nanoparticles could be promising nano-drug delivery systems for successful management of melanoma.

The blood–brain barrier (BBB) restricts the transport of potential therapeutic moieties to the brain. Direct targeting the brain via olfactory and trigeminal neural pathways by passing the BBB has gained an important consideration for delivery of wide range of therapeutics to brain. Intranasal route of transportation directly delivers the drugs to brain without systemic absorption, thus avoiding the side effects and enhancing the efficacy of neurotherapeutics. Over the last several decades, different drug delivery systems (DDSs) have been studied for targeting the brain by the nasal route. Novel DDSs such as nanoparticles (NPs), liposomes and polymeric micelles have gained potential as useful tools for targeting the brain without toxicity in nasal mucosa and central nervous system (CNS). Complex geometry of the nasal cavity presented a big challenge to effective delivery of drugs beyond the nasal valve. Recently, pharmaceutical firms utilized latest and emerging nasal drug delivery technologies to overcome these barriers. This review aims to describe the latest development of brain targeted DDSs via nasal administration. Chemical compounds studied in this article Carbopol 934p (PubChem CID: 6581) Carboxy methylcellulose (PubChem CID: 24748) Penetratin (PubChem CID: 101111470 ) Poly lactic-co-glycolic acid (PubChem CID: 23111554) Tween 80 (PubChem CID: 5284448 )

Traditional cancer therapies carry a risk of serious side effects and toxicity. Developing an alternative treatment modality that is highly effective, has low toxicity and is noninvasive is urgently required. Here, we exploited molybdenum oxide (MoOx) nanosheets as a drug carrier and degradable photothermal agent to provide a chemo-photothermal combination cancer therapy. The MoOx nanosheets were synthesized by a one-pot hydrothermal method and then modified with pluronic F127 to improve physiological stability and biocompatibility. The F127-modified nanosheets (MoOX@F127) showed ultrahigh drug loading efficiency (DLE) of doxorubicin (DOX) (DLE%; 65%, W(load DOX)/[W(load DOX) + WMoOx@F127]), strong near-infrared (NIR) absorption and desirable pH-dependent degradability. After intravenous injection, MoOx@F127 nanosheets were degraded at physiological pH and were rapidly excreted from normal organs, while they were effectively accumulated and retained long-term in the more acidic tumor tissue. This simultaneously ensured effective tumor ablation after NIR irradiation and avoided long-term retention and toxicity in vivo. Compared to chemotherapy or photothermal therapy alone, in vitro and in vivo tumor ablation studies have shown a notably improved synergistic effect of the combination therapy. Our study presents a multifunctional nanosystem with a desirable degradability for chemo-photothermal combination cancer therapy that has great potential in biomedical applications.

The standard chemotherapy is facing the challenges of lack of cancer selectivity and development of drug resistance. Currently, with the application of nanotechnology, the rationally designed nanocarriers of chondroitin sulfate (CS) have been fabricated and their unique features of low toxicity, biocompatibility, and active and passive targeting made them drug delivery vehicles of the choice for cancer therapy. The hydrophilic and anionic CS could be incorporated as a building block into- or decorated on the surface of nanoformulations. Micellar nanoparticles (NPs) self-assembled from amphiphilic CS-drug conjugates and CS-polymer conjugates, polyelectrolyte complexes (PECs) and nanogels of CS have been widely implicated in cancer directed therapy. The surface modulation of organic, inorganic, lipid and metallic NPs with CS promotes the receptor-mediated internalization of NPs to the tumor cells. The potential contribution of CS and CS-proteoglycans (CSPGs) in the pathogenesis of various cancer types, and CS nanocarriers in immunotherapy, radiotherapy, sonodynamic therapy (SDT) and photodynamic therapy (PDT) of cancer are summarized in this review paper.

Paclitaxel (PTX) is one of the natural products used as first- or second-line treatment of cancer. It has a wide spectrum of activity against various cancer types, but low solubility in water, and toxicity to normal tissues such as hypersensitivity reaction and neuropathy limited its applications. The serious endeavors have been made to design and fabricate a more favorable nanoformulation lowering the inherent toxicity and side effects of PTX. The polymer-drug conjugates as a class of polymer-based nanomedicines have been reported to reduce adverse effects, enhance uptake and accumulation in tumor cells, potentiate therapeutic efficacy and improve patient compliance compared to polymer-encapsulated drugs. Collectively, very “old” PTX as cytotoxic drug bound to polymer has enormous potential and broad prospects. In this review, we mainly pay attention to summarize progress in the polymer-PTX conjugates designed and evaluated in recent decades to potentiate the therapeutic efficacy and tackle adverse effects of PTX.

AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the “multiple hit hypothesis” of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis.

Eosinophils are nonspecific harbingers of esophageal disease. We report on the incidence and features of esophageal eosinophilia diagnosed at our center in 2011 and compare the findings with previously published results between 1980-1988 and 2000-2002. Eosinophils per high-power field were counted in esophageal biopsies from 675 patients who underwent 710 endoscopic procedures between January 1, 2011, and December 31, 2011. Of these, 209 (33%) patients were infiltrated with eosinophils; the other 466 (67%) showed no pathological changes. The highest concentrations of eosinophils were observed in the distal esophagus. Our findings also indicate that esophageal eosinophilia fluctuates over time.

Celiac disease is a gluten enteropathy that is treated with dietary elimination of gluten. Exposure to nondietary sources of gluten, which are used in the manufacture of products such as plastics, dental equipment, and cosmetics, can also trigger or exacerbate disease. We report the case of a 9-year-old child who presented with nonspecific abdominal discomfort with abnormal serology for celiac disease. She underwent duodenal biopsies that revealed Marsh 3B histopathology. Despite strict dietary elimination of gluten, she continued to be symptomatic and demonstrate positive serum markers for active disease. It was then discovered that the child was exposed to gluten from her orthodontic retainer that contained a plasticized methacrylate polymer. Gluten is a common additive in plastics. She discontinued its use and demonstrated symptom resolution and complete normalization of serology. All possible sources of gluten, including nondietary, must be considered when managing a child with celiac disease.

Two hundred thirty-four cases of primary gastrointestinal tract malignancy were diagnosed at the histopathology laboratory of Asir Central Hospital over a four-year period, from 1987 to 1990. The current study is a retrospective analysis of these cases regarding rank orders, distribution according to nationality, age and sex, primary sites affected and the histopathologic pattern. Eighty-eight percent of our cases were Saudi and 12% were non-Saudi nationals. The mean age of patients was 60 +/- 16 years with a male:female ratio of 2:1. Primary liver cancer was the most common malignancy (29%), followed by gastric cancer (27%), colorectal cancer (21%) and esophageal cancer (13%). Comparison of our findings to those from other provinces of the Kingdom are also included.

OBJECTIVES It is not known whether the prevalence of childhood esophagitis has changed over time. In children, the intraepithelial eosinophil is considered the hallmark of esophageal inflammation. This study compares the prevalence of intraepithelial eosinophils in esophageal biopsies obtained from 1980-1988 and 2001-2002. PATIENTS AND METHODS This study reevaluated all of the esophageal biopsies obtained at a single center during 2 periods: 1980-1988 and 2001-2002. Histological appearances were characterized and eosinophils per high-power field were quantified. RESULTS In total, 1058 esophageal biopsies from 510 subjects were reviewed. Between 1980 and 1988, 247 biopsies from 188 subjects were evaluated. Of these, 62 subjects met the criteria for esophageal disease, and 106 had no specific pathological changes. Between 2001 and 2002, 811 biopsies from 322 subjects were evaluated. Of these, 132 subjects met the criteria for esophageal disease, and 182 had no specific pathological changes. A statistically significant increase in the prevalence of esophageal inflammatory disease was observed comparing the recent group with the remote group. Eosinophilic esophagitis is thought to be distinct from other types of esophagitis in pathogenesis, epidemiology, histology, and treatment. Some suggest the prevalence of eosinophilic esophagitis has increased in recent years. We sought evidence for an increase in histological changes consistent with eosinophilic esophagitis. No matter whether histology consistent with eosinophilic esophagitis was defined as 25, 20, 15, or 10 eosinophils per high-power field, no increase in prevalence was found. CONCLUSIONS This study demonstrated no evidence for a change in the density of eosinophilic infiltrates in esophageal biopsies during the 22-year study period. The study showed a statistically significant increase in the prevalence of esophageal inflammatory disease across the same period.

Six hundred ninety-seven histologically confirmed cases of cancer were seen in the three-year period, 1987 to 1989, at Asir Central Hospital in Abha, Saudi Arabia. Percentage (crude relative) frequencies of cancer at various sites were determined. The most common cancer sites among males were skin, liver, lymphoid tissue (i.e., non-Hodgkin's lymphomas), bladder,, blood (leukemias), stomach, colon, esophagus, central nervous system, and prostate. Skin cancer was also the most common cancer among females, followed by breast, lymphoid tissue (non-Hodgkin's lymphomas), blood (leukemias), thyroid, stomach, colon, oral cavity, esophagus, and cervix.

Exogenous lipoid pneumonia induced by modified animal fat (ghee) in 10 children is described. The initial presentation was of an acute or chronic pneumonia which proved refractory to anti-microbial chemotherapy. The radiological presentation varied from mild perihilar consolidation to diffuse and extensive bilateral involvement, particularly of the posterior lung segments. A history of administration of ghee provided the initial clue to the diagnosis, which was confirmed by demonstration of fat by bronchoalveolar lavage or by open lung biopsy. Eight of the 10 patients improved with either steroid therapy alone or steroids with resection of the most involved lung segments. One patient, who had extensive superinfection with Mycobacterium fortuitum, died. Lipoid pneumonia should be considered in the differential diagnosis of 'non-resolving' pneumonias in communities where the cultural practice of infant feeding with ghee is prevalent. Public awareness through health education about the potential hazards of this practice to infants and children can contribute to reduce the incidence of the problem.

We describe a 3-month-old male infant who presented with gross hematuria and was found to have a renal mass and a testicular mass representing these two entities. This is the first case report of these two lesions presenting concomitantly.

Snakes have intrathoracic stomachs and rachischisis-like spinal vertebrae. These anomalies are rare in babies and have not been previously described in combination in the English medical literature. Here we present 2 cases of total intrathoracic stomach with a foreshortened esophagus, cervical spine rachischisis, and splenic anomalies in newborns. Both had 46, XX karyotypes. The first case was initially treated with mobilization of the stomach into the abdomen. However, at 18 months the stomach was found to have retracted back into the thorax. Subsequently, the patient received a Collis gastroplasty and G-tube. Two-year follow-up is available. The second case exhibited the abovementioned anomalies along with absence of toes 3 and 4 on the right foot, and cardiac anomalies not compatible with life. The parents chose to withdraw support. The encountered abnormalities may be explained by a first trimester mesenchymal insult and share some similarities with the VACTERL association. In our experience, mobilization of the stomach into the abdomen without elongation of the esophagus will fail. If tolerated, the management of the intrathoracic stomach should include preoperative intragastric feedings to allow time for gastric enlargement followed by a Collis gastroplasty. The management of cervical rachischisis requires assessment of cervical spine stability and cervical immobilization. As other life-threatening birth defects may be present, thorough evaluation should be completed before counseling the families of the treatment options available.

Homogenates of the internal organs of partially and fully engorged females of the camel tick Hyalomma (Hyalomma) dromedarii were naturally infected with single, rod-shaped bacteria. Bacteriological tests identified these microorganisms as Escherichia coli; their confident limit of identification being 95%. Transmission electron microscopy examination has also identified their typical ultrastructural features.

Occupational exposure to silica is associated with clinical renal disease. 1 The nephrotoxicity due to silica is believed to be either due to putative immune complex deposition in the glomeruli 2 or to direct deposition of crystalline material in the interstitium. 3 We report a case in which both of these causative factors were operating at the same time. The patient had glomerular injury due to IgA deposits, accompanied by interstitial damage due to silica deposition.

A definitive diagnosis of tuberculoid and borderline tuberculoid leprosy is based on a demonstration of either acid-fast bacilli or nerve elements within the granulomas. On routine hematoxylin and eosin stains, the nerve fibers are not easily identifiable. In this study, we used S-100 protein to highlight the nerve elements and to count their numbers in leprosy and non-leprosy granulomas.Skin biopsy specimens from 15 cases of tuberculoid/borderline tuberculoid leprosy and 14 cases belonging to other granulomatous diseases of the skin were stained with S-100 protein. The surface area of all the biopsies was calculated and the number of nerve bundles stained with S-100 protein were counted in each specimen.The nerve bundles were 15 per cm 2 in leprosy cases, and 9.2 per cm2 in non-leprosy cases. In addition, the leprosy cases showed longer nerve twigs that were perpendicularly oriented to the skin surface.Immunostaining with S-100 facilitated detection of nerve elements in tuberculoid/borderline tuberculoid leprosy. Also, an increased number of nerve elements were found in leprosy granulomas when compared with non-leprosy granulomas (P=0.05).

The objective of this study was to determine the incidence of Helicobacter pylori infection in different age and sex groups from the southern region of Saudi Arabia, and to relate the results to the high incidence of gastric cancer in this region. The carcinogenic effect of H. pylori is considered to be age-dependent. H. pylori infection early in life predisposes patients to gastric cancer. In contrast, acquisition of infection later in life leads to development of duodenal ulcer. We studied 528 consecutive endoscopic biopsies over a period from March 1995 to August 1996. The presence or absence of H. pylori was tabulated according to age and sex of the patients. Three hundred and fifty-three (67%) of 528 patients were positive for H. pylori. There were 313 males, among whom 217 (69%) were positive. There were 215 females, among whom 136 (63%) were positive for H. pylori. The presence of H. pylori in various age groups was as follows: under 16 years, 62%; 16 to 25 years, 67%; 26-35 years, 69%; 36-45 years, 67%; 46-55 years, 66%; and 56 years and above, 65%. Statistical analysis revealed no significant difference between the groups. No significant rise in the infection rate was noted from childhood to advanced age. These data support the belief that H. pylori infection was acquired early in life, leading to multifocal gastritis and thus predisposing the patients to gastric cancer later in life. However, H. pylori may not be the single agent of gastric cancer inasmuch as the infection affects both genders equally, whereas gastric cancer has a male preference. Perhaps some additional factors augment the pivotal role of H. pylori.

Background. The clinical diagnosis of cutaneous leishmaniasis is confirmed by demonstrating the organism on a superficial smear or on a biopsy of the lesion. Misdiagnosis in a biopsy specimen may be due to scanty Leishmania organisms that may not be identified in histologic sections. Methods. Punch biopsies of skin lesions, suspected clinically to be cutaneous leishmaniasis, from 29 patients were taken. Touch smears on slides were air-dried, fixed with methyl alcohol, and stained with Giemsa stain. Results of routine histologic examination were then compared with those of touch preparation. Results. Twenty-one cases were positive for leishmaniasis. In 18 cases, the organisms were seen both in the biopsy and in the touch preparation. In three cases, the organisms were only identified on touch preparation. Conclusions. A touch preparation improves the sensitivity of the diagnosis of cutaneous leishmaniasis without incurring additional cost to the laboratory.

Superficial lymph node biopsies received over a four year-period, 1987 to 1990, at the histopathology laboratory of Asir Central Hospital wre reviewed. Total number of patients was 324, all presented with peripheral lymphadenopathy as the primary sign. Two hundred sixty-six patients (82%) were Saudi nationals and 58 patients (18%) were non-Saudi nationals living in Asir region. Granulomatous lymphadenitis was the most common pattern (43%) followed by: nonspecific lymphoid hyperplasia (33%), malignant lymphoma (13%), metastatic nonlymphoid malignant neoplasm (6.6%), and miscellaneous specific lymphadenopathies (4.4%). The distribution patterns of various histopathologic findings according to age, sex, nationality and lymph node location are included.

Relative merits of three methods of diaphragmatic hernia repair were evaluated in growing animals. Twenty-five puppies underwent laparotomy. In four controls, the left hemidiaphragm was incised and sutured primarily. In the remaining dogs, it was partially resected sparing the phrenic nerve. The defects were repaired in six with silastic sheeting, in eight with polytetrafluoroethylene (PTFE; trademark, Gore-Tex), and in seven with a thoracoabdominal muscle flap. Dogs were killed at 1, 4, and 7 months for gross and microscopic evaluation of the repair. Diaphragmatic function was evaluated by inspiratory force against a closed airway and by selective phrenic nerve stimulation (PNS). Serial fluoroscopy was used to evaluate diaphragmatic motion. Grossly the diaphragms in all groups showed compensatory growth. Microscopically the silastic was encapsulated without adherence, while PTFE showed tissue ingrowth. Maximal inspiratory force was equivalent in all groups but selective PNS revealed left-sided impairment in all experimental groups. Fluoroscopy showed paradoxical motion of the diaphragm in the muscle flap group for 1 to 2 months, and in the silastic repair group for 2 to 3 weeks, with near normal motion in the PTFE group for the entire postoperative period. These differences disappeared by 6 months. Prosthetic materials or muscle flaps are all safe for repair of large diaphragmatic hernias. Diaphragmatic growth occurs and the prosthesis remains in place. Physiologic impairment is minimal and not of clinical importance. Use of PTFE may be the preferred method as it develops better tissue incorporation and results in more normal diaphragmatic motion in the critical early postoperative period.

A total of 110 reimplanted ureters from 61 patients were examined by light microscopy. Twenty-four distal segments from nonrefluxing ureters were used as control group. Overall, 55 of 110 specimens (50%) had inflammatory cell infiltrates (ICI) consisting of lymphocytes and plasma cells in the submucosa and adjacent muscularis. Forty-five ureters (82%) had mild ICI, and 10 ureters (18%) had moderate or severe ICI only in patients with history of infection. ICI increased with grade of reflux in both infected and noninfected groups. Of 75 ureters (68%) from patients with history of infection, 45 (60%) had ICI. Ten of 35 ureters (29%) from patients without history of infection had ICI. A causal relationship between reflux and ICI remains speculative and needs further study.

This article describes a metastasizing tumor of the paratesticular tissue which has features similar to that of malignant mesothelioma commonly seen in other mesothelial surfaces. The tumor is composed of two types of cells, epithelial-like and spindle-shaped malignant cells.

The immunomodulator Corynebacterium parvum stimulates the reticuloendothelial system and causes splenic hypertrophy. The ability of C parvum to stimulate splenic regeneration in hemisplenectomized mice and decrease susceptibility to intranasal pneumococcal challenge was studied. Mice were divided into two groups, control sham-operated (n = 48) and hemisplenectomized (n = 47) animals. Ten days later, each group was divided into two subgroups, those injected with C parvum (700 mcg IVP) and those injected with an equivalent volume of saline. The animals were challenged with Streptococcus pneumoniae, which was injected into one nostril three weeks postoperatively, and mortality was assessed. Four and one-half weeks postoperatively, splenic tissue was removed, measured, weighed, and submitted for histologic examination. The number of spleen cells per gram of tissue was assessed. Treatment with C parvum resulted in a significant increase in the splenic weight in both hemisplenectomized and control animals compared to similar saline-injected mice (P less than 0.001). The percentage increase in spleen weight of hemisplenectomized mice (106%) was significantly greater than that for control animals (56%; P less than 0.01). There was no significant difference among experimental groups in the number of spleen cells per gram of splenic tissue or in the histologic characteristics, indicating that C parvum stimulated relatively normal splenic growth. Survival following pneumococcal challenge was significantly increased for hemisplenectomized mice by C parvum treatment to a level that did not significantly differ from control mice. This study demonstrates that in mice the deficits related to resistance to infection and spleen size following hemisplenectomy are significantly improved by treatment with C parvum.